Ketorolac Ceiling Dose Implementation in

the Emergency Department

Abigail Geyer, PharmD

PGY1 Pharmacy Resident
Parkview Health | Fort Wayne, Indiana

Mentors: Jamie Gaul, PharmD, BCPS

Jim Roy, PharmD, BCCCP
Aaron Daseler, PharmD, BCCCP
Parkview Health | Fort Wayne, Indiana

The speaker and mentors have no actual or potential conflict of interest in relation to this presentation.
Background: Ceiling Effect with NSAIDs

• Nonsteroidal anti-inflammatory drugs

(NSAIDs) are known to have a "ceiling dose“
• Most effective dose for treatment
• Above the ceiling dose: 
• No further pain relief 
• More adverse effects

Motov. Ann Emerg Med. 2017 Aug;70(2):177-84. 

 Background: Ketorolac
Class:

• NSAID
• Reversible binding
• Nonselective COX-1 and COX-2 inhibitor

Indications for use:

• Approved: acute pain, short-term pain relief

• Off-label: migraine, severe acute pain

Administration:

• Oral (PO)
• Intramuscular (IM)
• Intravenous (IV)

Product Information: Ketorolac Tromethamine Injection. Hospira, Inc

(per manufacturer), Lake Forest, IL 60045, 2020. 
 Background: Ketorolac Dosing

Weight ≥50 kg and <65 years of age:

• IV: 30 mg as a single dose or 15 to 30 mg every 6 hours as needed; maximum

daily dose: 120 mg/day
• IM: 30 to 60 mg as a single dose or 15 to 30 mg every 6 hours as needed;
alternatively, may administer 10 to 30 mg every 4 to 6 hours as needed

Weight <50 kg or ≥65 years of age:

• IV: 15 mg as a single dose or 15 mg every 6 hours as needed; maximum daily

dose: 60 mg/day
• IM: 30 mg as a single dose or 15 mg every 6 hours as needed; alternatively,
may administer 10 mg every 4 to 6 hours as needed

Renal Dose Adjustments:

• eGFR 10 to 50 mL/minute/1.73 m2
• Some experts recommend avoiding use
• Consider 7.5 to 15 mg every 6 hours

Product Information: Ketorolac Tromethamine Injection. Hospira, Inc

(per manufacturer), Lake Forest, IL 60045, 2020. 
 Background: Concerns with Use

• Appropriate use– short term (up to 5 days) for the

management of moderately severe acute pain that requires
analgesia at the opioid level
• Box Warnings for NSAIDs:
• Cardiovascular thrombotic events
• Gastrointestinal (GI) risk– causes peptic ulcers, GI
bleeding, and/or perforation of stomach or intestines
• Renal risk– Contraindicated in advanced renal impairment
and in patients at risk for renal failure due to volume
depletion, acute kidney injury

Product Information: Ketorolac Tromethamine Injection. Hospira, Inc

(per manufacturer), Lake Forest, IL 60045, 2020. 
SUPPORTING LITERATURE
 Motov et al.
Motov et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for
Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial

Study Design Randomized, double-blind study conducted at a 711-bed urban community

teaching hospital
Inclusion/Exclusion Adults 18 to 65 years old
Acute pain (intensity 5)
Routinely be treated with
ketorolac
Active peptic ulcer disease, acute GI
hemorrhage, history of renal/hepatic
insufficiency
Allergy to NSAID
Unstable vital signs
Previous analgesic medication received

Outcomes Primary: Secondary:

Reduction in pain score at 30 Rates and percentages of subjects
minutes from medication experiencing adverse effects and requiring
administration rescue analgesia

Interventions Ketorolac 10, 15, 30 mg IV

Motov. Ann Emerg Med. 2017 Aug;70(2):177-84. 

 Motov et al.
Motov et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for
Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial

Baseline 240 total patients– 80 assigned to each group (10, 15, 30 mg IV ketorolac)
Characteristics Mean ages 41.5, 40.1, and 38.8 years old
% Male 39, 32, 37
Results Pain Scores at 30 Minutes 10 mg (N=80) 15 mg (N=80) 30 mg (N=80)
Baseline, mean 7.7 7.5 7.8

30 minutes post administration, mean 5.2 5.1 4.8

• There was no difference in pain score reduction from baseline to 30 minutes
across the 3 dose groups
There was no difference in rates of rescue medication use (morphine) across the
3 treatment groups
• At 30-minute follow-up, 5%, 3.8%, and 5% of patients in the 10, 15, and 30 mg
group received rescue medication
Safety: There was no difference in rates of adverse events reported (nausea,
dizziness, headache)

Motov. Ann Emerg Med. 2017 Aug;70(2):177-84. 

 Soleyman-Zomalan et al.
Soleyman-Zomalan et al. Patterns of Ketorolac Dosing by Emergency Physicians
Study Design Single center retrospective, descriptive study
Purpose Characterize patterns of ketorolac administration in ED patients at an urban New
York City community teaching hospital from 2003 to 2013
Results 49,606 ketorolac administration given to 34,026 patients
IV IM

Total administrations 38,688 9,916

Dosing
10 mg 203 (0.5%) 361 (3.7%)
15 mg 5,288 (13.67%) 102 (1.02%)
30 mg 32,715 (84.56%) 4,916 (49.57%)
60 mg 15 (0.03%) 4,553 (45.92%)
Most common diagnoses at discharge were renal colic (21%), low back pain
(17%), and abdominal pain (11%)

Key Points Ketorolac was prescribed above ceiling dose in 97% of patients who received IV
route and in 96% of patients who received IM route
Self-Assessment Question #1
Ketorolac is a/an _______ COX ______ inhibitor
A.Reversible, COX-2 selective
B.Irreversible, COX-2 selective
C.Irreversible, COX-1 and -2 nonselective
D.Reversible, COX-1 and -2 nonselective
Self-Assessment Question #2
The duration of ketorolac use should be limited to how
many days due to risk of adverse events:
A.3 days
B.5 days
C.7 days
D.10 days
Purpose
To evaluate change in pain scores after
implementing a ketorolac ceiling dose for
both IV and IM doses compared to
previous standard dosing in the emergency
department (ED).
 Setting
• Parkview Health
• Not-for-profit, community-
owned organization
• Northeast Indiana and
northwest Ohio
• 10 hospital health system
• Emergency departments
• Parkview Regional Medical
Center (PRMC)
• Parkview Hospital Randallia
(PVH)
Ordering at PRMC and PVH ED
Doses ranging from 10 to 60 mg

Both IV and IM routinely used

• IV use is more common than IM

• Higher 60 mg dose more common with IM
administration

30 mg dose was ordered most often

Intervention
• Ketorolac ceiling dose of 15 mg for
intravenous and intramuscular routes
• Provided written education to ED staff
• Removed personal order preferences for
ketorolac
• Established high dose warning and soft stop
for ketorolac orders > 15 mg
Design
• Retrospective study
• Multicenter
• Ceiling dose established at all Parkview
locations
• Only evaluating PRMC and PVH

Pre-Implementation Post-Implementation
Usual/Standard ED dosing practices Ketorolac 15 mg ceiling dose
July 1, 2021-October 26, 2021 October 27, 2021-January 31, 2022
Design

Inclusion Criteria Exclusion Criteria

• Adults ≥ 18 years old • Received analgesic

presenting to the medication in the ED
emergency prior to ketorolac
department  • Missing pain scores
• Acute pain
• Received ketorolac
IV/IM
Endpoints
• Primary
• Evaluate change in pain scores after receiving
ketorolac pre-implementation and post-
implementation
• Secondary
• Rescue medication use
• Admission vs discharge
• Medication prescribed at discharge from ED
• Initial inpatient medications ordered for pain
• Change in serum creatinine for admitted patients
 Patient Inclusion
Pre-Implementation Post-Implementation

3612 doses of 3049 doses of

ketorolac IV/IM ketorolac IV/IM

814 excluded due 762 excluded due

to receiving prior to receiving prior
analgesic 274 excluded for analgesic 69 excluded for
medication lack of baseline medication lack of baseline
pain score pain score

1938 excluded for 1533 excluded for

lack of follow-up lack of follow-up
pain score pain score

586 ketorolac 585 ketorolac

doses meeting doses meeting
inclusion criteria inclusion criteria
Baseline Characteristics
Pre-Implementation Post-Implementation
(N=586) (N=585)
Age, yrs, median (range) 39 (18-86) 37 (18-85)
Female sex, no. (%) 375 (64) 390 (66.6)
Weight, kg, median (range) 84.8 (35.4-245.8) 85.3 (43.1-256.3)
Baseline Creatinine, mg/dL,
median (range) 0.80 (0.44-2.22) 0.80 (0.41-2.01)

Ketorolac doses, no. (%)

• 15 mg 194 (33.1) 433 (74)
• 30 mg 351 (59.9) 145 (24.8)
• 60 mg 41 (7) 7 (1.2)
Intravenous, no. (%) 447 (76.3) 430 (73.5)
Intramuscular, no. (%) 139 (23.7) 155 (26.5)
 Baseline Characteristics

Pre-Implementation Post-Implementation
(N=586) (N=585)
Past Medical History, no. (%)
• Cardiac Condition 85 (14.5) 72 (12.3)
• Chronic Pain 15 (2.5) 3 (0.5)
• Chronic Kidney Disease (CKD) 4 (0.7) 8 (1.4)
Prior to Admission Medications,
no. (%)
• ACE-I 42 (7.2) 35 (6.0)
• ARB 30 (5.1) 39 (6.7)
• Diuretic 64 (10.9) 57 (9.7)
• NSAID 83 (14.2) 199 (34)
• Opioid 38 (6.5) 154 (26.3)
• Acetaminophen 11 (1.9) 31 (5.3)
Baseline Characteristics
Most Common ED Chief Complaints

Pre-Implementation Post-Implementation

107
135

224

266

88

86

73
56
85
51
Results– Primary Endpoint

Pre-Implementation Post-Implementation
(N=586) (N=585)

Baseline Pain Score,

Median (range) 8 (0-10) 8 (0-10)

Post-Ketorolac Pain Score,

Median (range) 5 (0-10) 5 (0-10)

Change in Pain Score 3 3

Ketorolac Dose, no. (%)
• 15 mg 194 (33.1) 433 (74)
• 30 mg 351 (59.9) 145 (24.8)
• 60 mg 41 (7) 7 (1.2)
Results– Secondary Endpoint
Pre-Implementation Post-Implementation
(N=586) (N=585)
Required Rescue Medication, no. (%) 130 (22.8) 121 (20.7)

Rescue Medication Use

155

90

65
58

33 36
22
17 16
0 2 2 1 2 3
PO Opioid IV Opioid NSAID Acetaminophen Other

Pre-Implementation Post-Implementation Total

 Results– Secondary Endpoint
Pre-Implementation (N=586) Post-Implementation
(N=585)
Discharged from ED, no. (%) 535 (91.3) 523 (89.4)
Discharged with Analgesic 87 (16.3) 145 (27.7)
Medication, no. (%)

Analgesic Medication Ordered for Discharge from ED

Acetaminophen

NSAID

Opioid

Other

0 20 40 60 80 100 120 140 160

Pre-Implementation Post-Implementation
 Results– Secondary Endpoint
Pre-Implementation (N=586) Post-Implementation
(N=585)
Admitted, no. (%) 51 (8.7) 65 (10.6)
Patients with Analgesic 35 (68.6) 30 (46.2)
Medication Ordered, no. (%)

Initial Analgesic Medication Ordered for Inpatient Use

Acetaminophen

NSAID

Opioid

Other

0 10 20 30 40 50 60 70

Pre-Implementation Post-Implementation
 Results– Secondary Endpoint

Pre-Implementation Post-Implementation
(N=16) (N=19)
Serum Creatinine, baseline
(mg/dL), median (range) 0.95 (0.48-1.63) 0.81 (0.6-1.41)

Serum Creatinine, Day 2 of

Admission (mg/dL), median (range) 0.89 (0.42-3.61) 0.72 (0.44-1.24)

Change in Serum Creatinine

(mg/dL) -0.06 -0.09
Conclusion and Future Direction
• One-time doses of IV/IM ketorolac 15 mg provided
similar results for:
• Pain relief
• Need for rescue medication
• Post-implementation included more post-dose pain
scores
• No conclusion regarding safety can be drawn
• Future direction
• Expanding the ceiling dose system wide
References
• Product Information: Ketorolac Tromethamine Injection. Hospira, Inc
(per manufacturer), Lake Forest, IL 60045, 2020.
• Eidinejad L, Bahreini M, Ahmadi A, et al. Comparison of intravenous
ketorolac at three doses for treating renal colic in the emergency
department: a noninferiority randomized controlled trial. Acad Emerg Med.
2021;00:1-8.
• Motov S, Yasavolian M, Likourezos A, et al. Comparison of
intravenous ketorolac at three single-dose regimens for treating
acute pain in the emergency department: a randomized controlled
trial. Ann Emerg Med. 2017 Aug;70(2):177-84.
• Soleyman-Zomalan E, Motov S, Likourezos A, et al. Patterns of
ketorolac dosing by emergency physicians. World J Emerg Med.
2017;8(1):43-6.